Background: Prolonged exposure (PE) is an effective treatment for post-traumatic stress disorder (PTSD).Objective: This study aimed to analyse the cost-effectiveness of three exposure-based... Show moreBackground: Prolonged exposure (PE) is an effective treatment for post-traumatic stress disorder (PTSD).Objective: This study aimed to analyse the cost-effectiveness of three exposure-based treatments in patients with childhood abuse-related PTSD.Method: A net–benefit analysis was conducted alongside a pragmatic randomized controlled trial with participants (N = 149) randomized to three conditions: PE (n = 48), intensified PE (i-PE, n = 51), and phase-based PE [Skills Training in Affective and Interpersonal Regulation (STAIR) + PE, n = 50]. Assessments took place at baseline (T0), post-treatment (T3), 6 month follow-up (T4), and 12 month follow-up (T5). Costs stemming from healthcare utilization and productivity losses were estimated using the Trimbos/iMTA questionnaire for Costs associated with Psychiatric Illness. Quality-adjusted life-years (QALYs) were based on the 5-level EuroQoL 5 Dimensions (EQ-5D-5L) using the Dutch tariff. Missing values of costs and utilities were multiply imputed. To compare i-PE to PE and STAIR + PE to PE, pair-wise unequal-variance t-tests were conducted. Net–benefit analysis was used to relate costs to QALYs and to draw acceptability curves.Results: Intervention costs did not differ across the three treatment conditions. Total medical costs, productivity losses, total societal costs, and EQ-5D-5L-based QALYs did not differ between treatment conditions either (all p > .10). At the relevant €50,000/QALY threshold, the probability of one treatment being more cost-effective than another was 32%, 28%, and 40% for PE, i-PE, and STAIR-PE, respectively.Conclusion: Three equally effective treatments were compared and no differences in cost-effectiveness between treatments were found. Therefore, we advocate the implementation and adoption of any of the treatments and endorse shared decision making. Show less
Nimphy, C.A.; Elzinga, B.M.; Does, W. van der; Aktar, E. 2022
Introduction Theoretical and empirical evidence suggests that the effect of parental verbal threat information on the offspring's fear acquisition of novel stimuli may be causal. The current study... Show moreIntroduction Theoretical and empirical evidence suggests that the effect of parental verbal threat information on the offspring's fear acquisition of novel stimuli may be causal. The current study investigated this verbal fear acquisition pathway from parents to children in the unique context of Covid-19 as a novel environmental threat for parents and children. Methods Using an online cross-sectional survey, we collected data about fear of Covid-19, parent-child communication, parental anxiety, and child temperament, in the period between June 11th 2020 and May 28th 2021. Participants were 8 to 18-year-old children (N = 195; M-age = 14.23; 113 girls) and their parents (N = 193; M-age = 47.82; 146 mothers) living in the Netherlands. Results Children of parents with stronger Covid-19 fears also reported stronger Covid-19 fears. Moreover, parents who were more fearful of Covid-19 provided more threat-related information about the virus to their children. More parental threat information in turn was related to stronger fear of Covid-19 in their children, and partly mediated the link between parent and child fear of the virus. The link between parental threat information and children's fear of Covid-19 was not moderated by child temperament or parental anxiety. Conclusions Parental communication about Covid-19 may play a role in children's fear acquisition of Covid-19. The lack of moderation of this link by parental anxiety and child temperament may reflect the potentially adaptive nature of verbal fear transmission during the first year of the pandemic and the nonclinical levels of fear in this community sample. Show less
Memarpouri, A.; Does, W. van der; Molendijk, M.L. 2022
There is growing evidence that change in distress is an indicator of change during Prolonged Exposure (PE) for post traumatic stress disorder (PTSD). However, temporal sequencing studies... Show moreThere is growing evidence that change in distress is an indicator of change during Prolonged Exposure (PE) for post traumatic stress disorder (PTSD). However, temporal sequencing studies investigating whether change in distress precedes PTSD symptom decline are lacking. These studies are essential since the timeline between indicators of change and treatment outcome is a key assumption for mediation. The aim of the present study was to assess the temporal relationship between within-and between session change in subjective distress and PTSD symptom decrease. We analyzed session data from 86 patients with PTSD. Data were analyzed using dynamic panel models. We distinguished temporal effects (within-persons) from averaged effects (between-persons). Results regarding the temporal effect showed that within-session change in subjective distress preceded PTSD symptom improvement while the reversed effect was absent. Averaged within session change in subjective distress was also related to PTSD symptom improvement. Results regarding the temporal effect of between-session change in subjective distress showed that it did not precede PTSD symptom improvement. Averaged between-session change in subjective distress was related to PTSD symptom improvement. This study provides evidence for within-but not between session change in subjective distress as indicator of change during PE. We also found that the way of modeling potential indicators of change affects results and implications. We recommend future studies to analyze mediators during treatment using temporal rather than averaged effects. Show less
Kivela, L.; Mouthaan, J.; Does, W. van der; Antypa, N. 2022
Background: The psychological well-being of students may be especially affected by the COVID-19 pandemic; international students can lack local support systems and represent a higher risk subgroup.... Show moreBackground: The psychological well-being of students may be especially affected by the COVID-19 pandemic; international students can lack local support systems and represent a higher risk subgroup. Methods: Self-reported depressive symptoms, suicidal ideation, anxiety, post-traumatic stress disorder (PTSD), insomnia, alcohol use, academic stress, and loneliness were examined in two cohorts of university students (March 2020 n = 207, March 2021 n = 142). We investigated differences i) between 2020 and 2021, ii) between domestic and international students, and ii) whether differences between the two cohorts were moderated by student status. Results: More depressive symptoms, academic stress, and loneliness were reported in 2021. International students reported more depressive symptoms, suicidal ideation, anxiety, PTSD, academic stress, and loneliness. The main effect of cohort was not moderated by student status. Conclusions: International students had worse mental health outcomes overall, but were not affected more by the COVID-19 pandemic than domestic students. Show less
Eveningness is associated with lower daily positive affect (PA). The relationship between negative affect (NA) and chronotype, however, is less consistent in the literature. Eveningness may be... Show moreEveningness is associated with lower daily positive affect (PA). The relationship between negative affect (NA) and chronotype, however, is less consistent in the literature. Eveningness may be further characterized by increased social isolation, which could explain the associations between chronotype and PA/NA. In the present longitudinal study, we used ecological momentary assessment (EMA) to investigate the associations of chronotype with daily PA, NA, and social contact in individuals with current and remitted major depressive disorder (MDD) and healthy controls. As part of the Netherlands Study of Depression and Anxiety (NESDA), 279 participants (n = 49 depressed, n = 172 remitted, n = 58 controls) monitored daily PA, NA, and social contact (i.e., being alone vs. with others) for two weeks, five times per day. Overall, eveningness was associated with less social contact. This effect became nonsignificant, however, after accounting for sociodemographics (gender, age, education, living situation). Chronotype was not related to PA or NA. Less social contact was associated with lower PA and higher NA independent of chronotype. In conclusion, we could not replicate the finding of lower PA among evening types, but found social contact to associate with both daily PA and NA. Show less
Struijs, S.Y.; Jong, P.J. de; Jeronimus, B.F.; Does, W. van der; Riese, H.; Spinhoven, P. 2021
Background: The Netherlands Study of Depression and Anxiety (NESDA; Nbaseline=2981) is an ongoing longitudinal, multi-site, naturalistic, cohort study examining the etiology, course, and... Show moreBackground: The Netherlands Study of Depression and Anxiety (NESDA; Nbaseline=2981) is an ongoing longitudinal, multi-site, naturalistic, cohort study examining the etiology, course, and consequences of depression and anxiety. In this article we synthesize and evaluate fifteen years of NESDA research on prominent psychological risk factors for the onset, persistence, recurrence, and comorbidity of affective disorders.Methods: A narrative review of 62 NESDA articles examining the specificity and predictive value of neuroticism, behavioral inhibition, repetitive negative thinking, experiential avoidance, cognitive reactivity, locus of control, (implicit) self-esteem, (implicit) disorder-specific self-associations, and attentional bias for the course of affective disorders.Results: All self-reported risk factors showed cross-sectional relationships with singular and comorbid affective disorders, and prospective relationships with the development and chronicity of depression and anxiety disorders. High neuroticism, low self-esteem, and negative repetitive thinking showed most prominent transdiagnostic relationships, whereas cognitive reactivity showed most pronounced depression-specific associations. Implicit self-esteem showed predictive validity for the persistence and recurrence of anxiety and depression over and above self-reported risk factors. Automatic approach-avoidance behavior and attentional bias for negative, positive, or threat words showed no relationship with affective disorders.Conclusion: NESDA identified both (a) transdiagnostic factors (e.g., neuroticism, low implicit self-esteem, repetitive negative thinking) that may help explain the comorbidity between affective disorders and overlap in symptoms, and (b) indications for disorder-specific risk factors (e.g., cognitive responsivity) which support the relevance of distinct disorder categories and disorder-specific mechanisms. Thus, the results point to the relevance of both transdiagnostic and disorder-specific targets for therapeutic interventions. Show less
Molendijk, M.L.; Molero, P.; Thomas-Odenthal, F.; Does, W. van der 2021
Background: One reason for the inclusion of Complex Posttraumatic Stress Disorder (CPTSD) in the 11th revision of the International Classification of Diseases (ICD-11) was its suspected relevance... Show moreBackground: One reason for the inclusion of Complex Posttraumatic Stress Disorder (CPTSD) in the 11th revision of the International Classification of Diseases (ICD-11) was its suspected relevance for treatment indications. We investigated whether CPTSD predicted and moderated treatment outcomes of Prolonged Exposure (PE), intensified PE (iPE) and Skills Training in Affective and Interpersonal Regulation followed by PE (STAIR + PE). We expected that CPTSD would predict worse treatment outcomes across treatments. Secondly, we expected that CPTSD would lead to better treatment effect in STAIR + PE compared to PE and iPE.Methods: We analyzed 149 patients with childhood-abuse related PTSD from a randomized clinical trial. CPTSD diagnosis and symptom severity were measured with the International Trauma Questionnaire. The main outcome was change in clinician-assessed PTSD symptoms. Assessments took place at baseline, week 4, week 8, week 16 (post-treatment) and at a 6-and 12-month follow-up. Analyses were based on an intention-to-treat sample using mixed effect models.Results: More than half (54 %) of the patients met criteria for CPTSD at baseline. CPTSD was related to more severe PTSD symptoms and higher comorbidity at baseline. CPTSD neither predicted nor moderated treatment outcome. Limitations: Inclusion was limited to patients with PTSD related to childhood abuse. Replication is needed in different samples.Conclusions: CPTSD is associated with more severe PTSD and with higher comorbidity. CPTSD did not predict treatment outcome and did not indicate differential treatment outcome of STAIR + PE compared to PE and iPE. Show less
Oprel, D.A.C.; Hoeboer, C.M.; Schoorl, M.; Kleine, R.A. de; Cloitre, M.; Wigard, I.G.; ... ; Does, W. van der 2021
Background: It is unclear whether the evidence-based treatments for PTSD are as effective in patients with CA-PTSD.Objective: We aimed to investigate the effectiveness of three variants of... Show moreBackground: It is unclear whether the evidence-based treatments for PTSD are as effective in patients with CA-PTSD.Objective: We aimed to investigate the effectiveness of three variants of prolonged exposure therapy.Method: We recruited adults with CA-PTSD. Participants were randomly assigned to Prolonged Exposure (PE; 16 sessions in 16 weeks), intensified Prolonged Exposure (iPE; 12 sessions in 4 weeks followed by 2 booster sessions) or a phase-based treatment, in which 8 sessions of PE were preceded by 8 sessions of Skills Training in Affective and Interpersonal Regulation (STAIR+PE; 16 sessions in 16 weeks). Assessments took place in week 0 (baseline), week 4, week 8, week 16 (post-treatment) and at a 6-and 12-month follow-up. The primary outcome was clinician-rated PTSD symptom severity.Results: We randomly assigned 149 patients to PE (48), iPE (51) or STAIR+PE (50). All treatments resulted in large improvements in clinician assessed and self-reported PTSD symptoms from baseline to 1-year follow-up (Cohen's d > 1.6), with no significant differences among treatments. iPE led to faster initial symptom reduction than PE for self-report PTSD symptoms (t(135) = -2.85, p = .005, d = .49) but not clinician-assessed symptoms (t(135) = -1.65, p = .10) and faster initial symptom reduction than STAIR+PE for self-reported (t(135) = -4.11, p < .001, d = .71) and clinician-assessed symptoms (t(135) = -2.77, p = .006, Cohen's d = .48) STAIR+PE did not result in significantly more improvement from baseline to 1-year follow-up on the secondary outcome emotion regulation, interpersonal problems and self-esteem compared to PE and iPE. Dropout rates did not differ significantly between conditions.Conclusions: Variants of exposure therapy are tolerated well and lead to large improvements in patients with CA-PTSD. Intensifying treatment may lead to faster improvement but not to overall better outcomes.The trial is registered at the clinical trial registry, number NCT03194113, Show less
Thomas-Odenthal, F.; Molero, P.; Does, W. van der; Molendijk, M. 2020
Background The recommendations of experts who write review articles are a critical determinant of the adaptation of new treatments by clinicians. Several types of reviews exist (narrative,... Show moreBackground The recommendations of experts who write review articles are a critical determinant of the adaptation of new treatments by clinicians. Several types of reviews exist (narrative, systematic, meta-analytic), and some of these are more vulnerable to researcher bias than others. Recently, the interest in nutritional interventions in psychiatry has increased and many experts, who are often active researchers on this topic, have come to strong conclusions about the benefits of a healthy diet on depression. In a young and active field of study, we aimed to investigate whether the strength of an author's conclusion is associated with the type of review article they wrote. Methods Systematic searches were performed in PubMed, Web of Science, Cochrane Database of Systematic Reviews, and Google Scholar for narrative reviews and systematic reviews with and without meta-analyses on the effects of diet on depression (final search date: May 30(th), 2020). Conclusions were extracted from the abstract and discussion section and rated as strong, moderate, or weak by independent raters who were blind to study type. A benchmark on legitimate conclusion strength was based on a GRADE assessment of the highest level of evidence. This systematic review was registered with PROSPERO, number CRD42020141372. Findings 24 narrative reviews, 12 systematic reviews, and 14 meta-analyses were included. In the abstract, 33% of narrative reviews and 8% of systematic reviews came to strong conclusions, whereas no meta-analysis did. Narrative reviews were 8.94 (95% CI: 2.17, 36.84) times more likely to report stronger conclusions in the abstract than systematic reviews with and without meta-analyses. These findings were similar for conclusions in the discussion section. Narrative reviews used 45.6% fewer input studies and were more likely to be written by authors with potential conflicts of interest. A study limitation is the subjective nature of the conclusion classification system despite high inter-rater agreements and its confirmation outside of the review team. Conclusions We have shown that narrative reviews come to stronger conclusions about the benefits of a healthy diet on depression despite inconclusive evidence. This finding empirically underscores the importance of a systematic method for summarizing the evidence of a field of study. Journal editors may want to reconsider publishing narrative reviews before meta-analytic reviews are available. Show less
Hoeboer, C.M.; Kleine, R.A. de; Molendijk, M.L.; Schoorl, M.; Oprel, D.A.C.; Mouthaan, J.; ... ; Minnen, A. van 2020
Background Many patients with post-traumatic stress disorder (PTSD) experience dissociative symptoms. The question of whether these dissociative symptoms negatively influence the effectiveness of... Show moreBackground Many patients with post-traumatic stress disorder (PTSD) experience dissociative symptoms. The question of whether these dissociative symptoms negatively influence the effectiveness of psychotherapy for PTSD is unresolved. Aims To determine the influence of dissociative symptoms on psychotherapy outcome in PTSD. Method We conducted a systematic search in Cochrane, Embase, PILOTS, PsycINFO, PubMed and Web of Science for relevant clinical trials. A random-effects meta-analysis examined the impact of dissociation on psychotherapy outcome in PTSD (pre-registered at Prospero CRD42018086575). Results Twenty-one trials (of which nine were randomised controlled trials) with 1714 patients were included. Pre-treatment dissociation was not related to treatment effectiveness in patients with PTSD (Pearson's correlation coefficient 0.04, 95% CI -0.04 to 0.13). Between-study heterogeneity was high but was not explained by moderators such as trauma focus of the psychotherapy or risk of bias score. There was no indication for publication bias. Conclusions We found no evidence that dissociation moderates the effectiveness of psychotherapy for PTSD. The quality of some of the included studies was relatively low, emphasising the need for high-quality clinical trials in patients with PTSD. The results suggest that pre-treatment dissociation does not determine psychotherapy outcome in PTSD. Show less
Burger, A.M.; Does, W. van der; Brosschot, J.F.; Verkuil, B. 2020
Background: Signs and symptoms of psychopathology can be chronic but are generally regarded as less stable over time than markers of cognitive vulnerability and personality. Some findings suggest... Show moreBackground: Signs and symptoms of psychopathology can be chronic but are generally regarded as less stable over time than markers of cognitive vulnerability and personality. Some findings suggest that these differences in temporal stability are modest in size but a rigorous examination across concepts is lacking. The current study investigated the temporal stability of affective symptoms, cognitive vulnerability markers and personality traits at various assessments over nine years.Methods: Participants of the Netherlands Study of Depression and Anxiety were assessed at baseline and reassessed after 2, 4, 6 and 9 years. They were grouped on the basis of waves of depression and anxiety CIDI-diagnoses into stable healthy (n = 768), stable patients (n = 352) and unstable patients (n = 821). We determined temporal stability by calculating intraclass correlation coefficients (ICC) and consistency indices of latent state-trait analyses (LST).Results: Temporal stability was moderate to high for symptoms (range ICC's 0.54-0.73; range consistency 0.64-0.74), cognitive vulnerability (range ICC's 0.53-0.76; range consistency 0.60-0.74) and personality (range ICC's 0.57-0.80; range consistency.60 -0.75). Consistency indices for all measures were on average a bit lower in the unstable group (ICC = 0.54) compared to the stable groups (ICC = 0.61). Overall stability was similarly high after 2, 4, 6 and 9 years.Conclusion: The 9-year stability over time of symptoms of affective disorders and that of indices of cognitive vulnerability and personality are remarkably similar and relatively high. Show less
Kivela, L.; Krause-Utz, A.; Mouthaan, J.; Schoorl, M.; Kleine, R. de; Elzinga, B.; ... ; Antypa, N. 2019
Background: Prior research indicates that the factors that trigger suicidal ideation may differ from those that maintain it, but studies into the maintenance of suicidal ideation remain scarce. Our... Show moreBackground: Prior research indicates that the factors that trigger suicidal ideation may differ from those that maintain it, but studies into the maintenance of suicidal ideation remain scarce. Our aim was to assess the longitudinal course of suicidal ideation, and to identify predictors of persistent suicidal ideation.Methods: We used data from the Netherlands Study of Depression and Anxiety (NESDA). We performed a linear mixed-effects growth model analysis (n = 230 with current suicidal ideation at baseline) to assess the course of suicidal ideation over time (baseline through 2-, 4-, 6- and 9-year follow-up). We used logistic regression analysis (n = 195) to test whether factors previously associated with the incidence of suicidal ideation in the literature (insomnia, hopelessness, loneliness, borderline personality traits, childhood trauma, negative life events) also predict persistence of suicidal ideation (i.e., reporting ideation at two consecutive assessment points, 6-and 9-years). We controlled for socio-demographics, clinical diagnosis and severity, medication use, and suicide attempt history.Results: Suicidal ideation decreased over time, and this decrease became slower with increasing time, with the majority of symptom reductions occurring in the first two years of follow-up. More severe insomnia and hopelessness were associated with increased odds of persistent suicidal ideation, and hopelessness was a significant mediator of the relationship between insomnia and persistent suicidal ideation.Limitations: Findings may not generalize to those with more severe suicidal ideation due to dropout of those with the worst clinical profile.Conclusions: Targeting insomnia and hopelessness in treatment may be particularly important to prevent the persistence of suicidal ideation. Show less
Son, D. van; Rover, M. de; Blasio, F.M. de; Does, W. van der; Barry, R.J.; Putman, P. 2019
BackgroundPrior research indicates that the factors that trigger suicidal ideation may differ from those that maintain it, but studies into the maintenance of suicidal ideation remain scarce. Our... Show moreBackgroundPrior research indicates that the factors that trigger suicidal ideation may differ from those that maintain it, but studies into the maintenance of suicidal ideation remain scarce. Our aim was to assess the longitudinal course of suicidal ideation, and to identify predictors of persistent suicidal ideation.MethodsWe used data from the Netherlands Study of Depression and Anxiety (NESDA). We performed a linear mixed-effects growth model analysis (n = 230 with current suicidal ideation at baseline) to assess the course of suicidal ideation over time (baseline through 2-, 4-, 6- and 9-year follow-up). We used logistic regression analysis (n = 195) to test whether factors previously associated with the incidence of suicidal ideation in the literature (insomnia, hopelessness, loneliness, borderline personality traits, childhood trauma, negative life events) also predict persistence of suicidal ideation (i.e., reporting ideation at two consecutive assessment points, 6- and 9-years). We controlled for socio-demographics, clinical diagnosis and severity, medication use, and suicide attempt history.ResultsSuicidal ideation decreased over time, and this decrease became slower with increasing time, with the majority of symptom reductions occurring in the first two years of follow-up. More severe insomnia and hopelessness were associated with increased odds of persistent suicidal ideation, and hopelessness was a significant mediator of the relationship between insomnia and persistent suicidal ideation.LimitationsFindings may not generalize to those with more severe suicidal ideation due to dropout of those with the worst clinical profile.ConclusionsTargeting insomnia and hopelessness in treatment may be particularly important to prevent the persistence of suicidal ideation. Show less
Burger, A.M.; Diest, I. van; Does, W. van der; Korbee, J.N.; Waziri, N.; Brosschot, J.F.; Verkuil, B. 2019
Fear overgeneralization is thought to be one of the cardinal processes underlying anxiety disorders, and a determinant of the onset, maintenance and recurrence of these disorders. Animal studies... Show moreFear overgeneralization is thought to be one of the cardinal processes underlying anxiety disorders, and a determinant of the onset, maintenance and recurrence of these disorders. Animal studies have shown that stimulating the vagus nerve (VNS) affects neuronal pathways implicated in pattern separation and completion, suggesting it may reduce the generalization of a fear memory to novel situations. In a one-day study, 58 healthy students were subjected to a fear conditioning, fear generalization, and fear extinction paradigm. Participants were randomly assigned to receive either transcutaneous auricular VNS (tVNS; final N = 29) or sham stimulation (final N = 29) during the generalization and extinction phases. tVNS did not affect fear generalization, as reflected by US expectancy ratings and fear potentiated startle responses. However, participants who received tVNS reported lower US expectancy ratings to the CS + during the extinction phase, possibly reflecting a stronger declarative extinction of fear. No effects of tVNS on fear potentiated startle responses during extinction were found. The pattern of findings regarding extinction of declarative fear suggest a facilitating effect of tVNS. Show less
Burger, A.M.; Does, W. van der; Thayer, J.F.; Brosschot, J.F.; Verkuil, B. 2019
Worrying is a central component of anxiety disorders. We tested whether non-invasive vagus nerve stimulation reduces negative thought intrusions in high worriers. Worry was assessed with a... Show moreWorrying is a central component of anxiety disorders. We tested whether non-invasive vagus nerve stimulation reduces negative thought intrusions in high worriers. Worry was assessed with a Breathing Focus Task, which consists of a pre-worry period, a worry induction, and a post-worry period. Ninety-seven high worriers were randomly allocated to receive transcutaneous electrical stimulation of the auricular branch of the vagus nerve at the concha (tVNS), or of the earlobe (sham stimulation) throughout the lab session. Participants who received tVNS reported significantly fewer negative thought intrusions during the pre-worry period, but the effects of tVNS after the worry induction were mixed. An exploratory analysis indicated that participants in the tVNS condition were more likely to report negative thought intrusions shortly after the worry induction, but became less likely to do so as the post-worry period went on. No effects of tVNS on RMSSD were observed. These findings provide preliminary indications that tVNS may decrease the occurrence of worrisome thoughts. Show less
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